OBJECTIVE: The mechanism underlying the therapeutic effects of combi-molecule JDF12 on prostate cancer (PCa) DU145 cells remains still unclear. This study aimed to investigate the proteomic profile after JDF12 treatment in DU145 cells by comparing with that in Iressa treated cells and untreated cells. METHODS: MTT was used to evaluate drug cytotoxicity, DAPI staining was done to assess apoptosis of cells, and flow cytometry was used to analyze cell cycle. iTRAQ and qPCR were employed to obtain the proteomic profiles of JDF12 treated, Iressa treated, and untreated DU145 cells, and validate the expression of selected differentially expressed proteins, respectively...

Glioblastoma multiforme (GBM) is the most common and severe form of primary tumor in the central nervous system of adults which has poor prognosis and limited therapeutic options. Epidermal growth factor receptor (EGFR) inhibitor, such as gefitinib (brand name Iressa, ZD1839), has been approved as a targeted medicine for several types of tumor including glioblastoma multiforme. However, gefitinib exerted very limited effects on some glioblastoma multiforme patients after a period of treatment due to intrinsic and acquired drug resistance...

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC.A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed...

Gefitinib (Iressa, AstraZeneca) has been widely used for the treatment of locally advanced or metastatic non-small cell lung cancer. A number of studies have been reported on its pharmacokinetics profiles, especially on the metabolism. In this review, we have comprehensively summarized the pharmacokinetic characteristics of gefitinib: absorption, distribution, metabolism and excretion (ADME). Overall, gefitinib reached the maximum plasma level relatively fast and distributed extensively. It underwent extensive biotransformation and predominantly excreted in feces, with less than 7% in the urine...

EGF-mediated EGFR endocytosis plays a crucial role in the attenuation of EGFR activation by sorting from early endosomes to late endosomes and transporting them into lysosomes for the final proteolytic degradation. We previously observed that cathepsin S (CTSS) inhibition induces tumour cell autophagy through the EGFR-mediated signalling pathway. In this study, we further clarified the relationship between CTSS activities and EGFR signalling regulation. Our results revealed that CTSS can regulate EGFR signalling by facilitating EGF-mediated EGFR degradation...

BACKGROUND: For Glioblastoma (GBM) patients, a number of anti-neoplastic strategies using specifically targeting drugs have been tested; however, the effects on survival have been limited. One explanation could be treatment resistance due to redundant signaling pathways, which substantiates the need for combination therapies. In GBM, both the epidermal growth factor receptor (EGFR) and the notch signaling pathways are often deregulated and linked to cellular growth, invasion and angiogenesis...

Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917)...

Lung cancer is a malignancy with the highest incidence of morbidity and mortality worldwide. The lack of effective detection methods leads to the ineffectiveness of convetional therapy. The aim of the current study was to analyze the hydrothorax epidermal growth factor receptor (EGFR) mutation in patients with advanced non-small lung cancer (NSCLC) and malignant pleural effusion. A new method for clinical treatment was developed through a comparison of the difference of EGFR tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy...

Gefitinib (Iressa) is the first oral EGFR tyrosine kinase inhibitor and it brings benefits to non-small cell lung cancer patients with EGFR mutation. In this study, a simple, rapid and credible high performance liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous quantification of gefitinib and its main metabolites M523595, M537194, M387783 and M608236 in NSCLC tumor-bearing mouse plasma. Sample extraction was done by protein precipitation using acetonitrile containing dasatinib as the internal standard...

BACKGROUND: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned. PATIENTS AND METHODS: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue...

Gefitinib (Iressa) is a selective and potent EGFR tyrosine kinase inhibitor. It received an accelerated FDA approval in 2003 for the treatment of patients with nonsmall cell lung cancer (NSCLC) and represents the first-line therapy for NSCLC with EGFR mutations. In the work presented herein, the disposition of gefitinib was investigated extensively in mouse in both plasma and 11 organs (liver, heart, lung, spleen, gut, brain, skin, fat, eye, kidney, and muscle) after a single IV dose of 20 mg/kg. Gefitinib demonstrated extensive distribution in most tissues, except for the brain, and tissue to plasma partition coefficients (K pt) ranged from 0...

Gefitinib (Iressa, ZD-1839), a small molecule tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) pathway, is currently under investigation in clinical trials for the treatment of colorectal cancer (CRC). However, as known, some patients develop resistance to TKIs, and the mechanisms mediating intrinsic resistance to EGFR-TKIs in CRC have not been fully characterized. Resistance to EGFR inhibitors reportedly involves activation of signal transducer and activator of transcription 3 (STAT3) in glioma and lung cancer...

Novel saponins that retain a free carboxyl group at the C-17 position and various sugars linked at the C-3 position of hederagenin aglycone were synthesized via stereospecific glycosylation. Since these natural products represented by Pulsatilla saponin D (PSD) were obtained in very small amounts, the total synthesis developed in this paper will resolve this problem of scarcity. The two types of synthesized arabinose- and rhamnose-cored saponins showed potent anticancer activity against a human lung cancer cell line (A549), and most disaccharide moiety saponins possessed more potent anti-lung cancer activity...

Members of the Bcl-2 family are established regulators of cell death. However, recent studies have shown that they can also regulate cell migration, invasion, and cancer metastasis. These functions of cancer cells are promoted by pro-survival Bcl-2 proteins (Bcl-2, Bcl-XL, and Bcl-w) but are suppressed by pro-apoptotic members (Bax and Bak). We have previously shown that Bcl-w and Bcl-XL enhance the ability of respiratory complex-I to produce reactive oxygen species (ROS), stimulating the phosphoinositide 3-kinase (PI3K)-dependent invasion pathway...

OBJECTIVES: The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. MATERIALS AND METHODS: Our analysis compared the 'EGFR testing strategy', in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the 'no-testing strategy,' in which genetic testing was not conducted and all patients were treated with standard chemotherapy...